Osteopontin affects macrophage polarization promoting endocytic but not inflammatory properties

• Published in: Obesity (Silver Spring, Md.) Vol. 24; no. 7; pp. 1489 - 1498
• Main Authors: Schuch, Karina, Wanko, Bettina, Ambroz, Katharina, Castelo‐Rosa, Alexandra, Moreno‐Viedma, Verónica, Grün, Nicole G., Leitner, Lukas, Staffler, Günther, Zeyda, Maximilian, Stulnig, Thomas M.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2016
• Subjects: Adipocytes; Adipocytes - physiology; Adipose Tissue - metabolism; Animals; Cytokines; Dendritic cells; Diet; Diet, High-Fat; Genotype & phenotype; Inflammation; Inflammation - physiopathology; Insulin; Insulin Resistance; Macrophages - physiology; Male; Metabolic disorders; Mice; Mice, Inbred C57BL; Obesity; Obesity - physiopathology; Osteopontin - metabolism; Phagocytosis - physiology; Phenotype; Physiology; Signal transduction; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumors
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1002/oby.21510

Objective Macrophages are the main drivers of obesity‐induced adipose tissue (AT) inflammation that causes insulin resistance. Macrophages polarize toward different inflammatory (M1) or protective (M2) phenotypes. Osteopontin (OPN) is an inflammatory cytokine highly expressed in AT in obesity and known to be involved in chronic inflammatory processes. It was hypothesized that OPN polarizes macrophages into a proinflammatory phenotype. Methods AT macrophages (ATMs) of OPN‐deficient (Spp1−/−) and wild‐type C57BL/6 (WT) mice with obesity and bone marrow‐derived macrophages (BMDMs) of Spp1−/− and WT mice as well as human monocyte‐derived macrophages (MDMs) polarized in the presence of OPN were investigated. Results While ATM infiltration was lower in Spp1−/− upon high‐fat diet, Spp1−/− ATMs expressed more M1 and less M2 markers but less tumor necrosis factor‐α compared with WT. There was no effect of OPN deficiency on BMDM polarization. In human MDMs, the presence of OPN during polarization ambiguously altered M1/M2‐related marker expression and diminished LPS‐induced inflammatory cytokine production. Strikingly, phagocytic activity was elevated by the presence of OPN during polarization in both human MDMs and murine BMDMs. Conclusions In contradiction to our hypothesis, data indicated that OPN does not induce inflammatory macrophages but was a signal to induce phagocytosis, which may be required due to increased adipocyte death in obesity.